Cardiovascular disease, including myocardial infarction (MI) and stroke, is the leading cause of death for women in the United States. Subclinical hypothyroidism (SCH), in which thyroid hormone levels are in the normal range but thyroid stimulation hormone (TSH) is elevated, has been linked to abnormal lipid profiles, atherosclerosis, and MI. The literature is scant however, and the evidence constrained by small studies, many of cross-sectional design. Both the US Preventive Services Task Force and the Institute of Medicine recently concluded that current data are insufficient to inform clinical decision-making about the need for screening or treatment for SCH. Because SCH is more common among women and with advancing age, we seek to examine the association of SCH and risk of MI and stroke in a large prospective cohort of post-menopausal women. We propose an efficient case-cohort study within the 93,676-member Observational Study of the Women's Health Initiative, including 800 women who have experienced an MI, 750 with thrombotic/embolic stroke, and a randomly selected subcohort of 3,200 women density-matched for age, race/ethnicity, and clinical center. Participants have extensive baseline demographic, health, behavioral, and physical exam data and stored serum available. We will measure TSH and thyroid hormone levels in order to identify SCH at entry. Follow-up includes annual health status updates and a physical exam in the third year; more than or equal to 5 years have passed since enrollment for all women. Thus, using new laboratory studies and existing WHI data, we will be able to answer these primary research questions: Among women without a history of thyroid disease, MI, or stroke: 1) Is subclinical hypothyroidism at baseline independently associated with risk of MI? 2) Is subclinical hypothyroidism at baseline independently associated with risk of ischemic stroke 3) What form of association best describes the relationship between TSH, as a continuous measure, and risk of MI and stroke? 4) What are the population correlates (i.e., race/ethnicity, BMI, hormone therapy, comorbidity) of SCH? This information - currently unavailable for middle-aged and older women - is germane to public health and health care policy to define the burden of illness associated with SCH, and to quantify the benefits and costs of eventual population screening and treatment.